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Altered leukocyte response in relation to the basic abnormality in children with asthma and bronchial
Insights
Intrinsic cellular factors contribute to asthma. Asthmatic children showed higher leukocyte responsiveness, specifically superoxide anion generation and histamine release, compared to healthy children, indicating a basic intracellular abnormality.
Area of Science:
- Immunology
- Pulmonology
- Cell Biology
Background:
- Asthma pathogenesis involves environmental and intrinsic factors.
- Bronchial hyperresponsiveness (BHR) is a hallmark of asthma.
- Leukocyte function may play a role in BHR.
Purpose of the Study:
- To investigate the role of intrinsic cellular factors in BHR in asthmatic children.
- To compare leukocyte responsiveness in asthmatic children with high and low BHR versus healthy children.
Main Methods:
- Compared superoxide anion (O-2) generation and histamine release in leukocytes.
- Stimulated leukocytes using calcium ionophore A 12387 with calcium and deuterium oxide (D2O).
- Assessed BHR based on inhaled histamine and exercise response.
Main Results:
- Asthmatic children exhibited significantly greater O-2 generation and histamine release than healthy children.
- Children with high BHR showed greater histamine release than those with low BHR.
- Both O-2 generation and histamine release correlated significantly.
Conclusions:
- Suggests an intrinsic intracellular abnormality contributes to increased bronchial hyperresponsiveness in asthma.
- Leukocyte responsiveness is a potential indicator of asthma severity and underlying cellular mechanisms.
Abstract:
The hypothesis that bronchial hyperresponsiveness in asthma is influenced not only by environmental but also by intrinsic cellular factors was studied. We compared leukocyte responsiveness in asthmatic children with high (Group A) or low (Group B) bronchial responsiveness and in healthy children (Group C). Leukocyte responsiveness was assessed by the generation of superoxide anion (O-2) and the release of histamine after challenge with calcium ionophore A 12387 in the presence of calcium, and with deuterium oxide (D2O). Bronchial responsiveness was graded on the basis of response to inhaled histamine and exercise. The mean generation of O-2 and mean release of histamine by the calcium ionophore A 12387 and calcium were significantly greater in the asthmatics than in the healthy subjects (p less than 0.05). The mean release of histamine, but not the mean O-2 generation, was greater in Group A than in Group B (p less than 0.025). After D2O challenge a significant difference was found in the mean O-2 generation (p less than 0.05) and the mean histamine release (p less than 0.025) between asthmatic and healthy children. Between Groups A and B, the mean histamine release but not the O-2 generation was significantly different (p less than 0.025). The generation of O-2 and release of histamine were significantly correlated (r = 0.45, p less than 0.01). The results suggest that there is a basic intracellular abnormality that causes increased bronchial hyperresponsiveness.